Abstract
Purpose:
To evaluate the specific killing effect of the adenoviral vector in which CD ::upp genes were directed by the GSTP1 promoter on cisplatin-resistant ovarian cancer cells.
Experimental design:
Cisplatin-sensitive (A2780) and cisplatin-resistant (AD6) ovarian cancer cells were infected with recombinant adenoviral plasmid carrying the CD ::upp gene driven by the GSTP1 promoter and followed with 5-FC administration.
Results:
In vitro, when MOI was 100 and 5-FC was 250 microg/ml, relative survival rate of the AD6 cells was only 3.63 +/- 1.01%, while under the same conditions, A2780 cells were 76.50 +/- 2.81%. Significant bystander effect was caused by the CD ::upp gene and 20% of gene-transferred AD6 cells caused death to 80.3% of the total cells. Furthermore, a significant anti-tumor effect of the Ad.GST-CD ::upp/5-FC was observed in nude mice bearing tumors of AD6 cells.
Conclusions:
These results indicated that adenovirus-mediated Ad.GST-CD ::upp/5-FC directed by GSTP1 promoter is an effective approach to overcome cisplatin-resistant ovarian cancer.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenoviruses, Human / genetics
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Animals
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Antineoplastic Agents / pharmacology
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Artificial Gene Fusion
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Cell Growth Processes / drug effects
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Cell Line, Tumor
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Cisplatin / pharmacology*
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Cytosine Deaminase / genetics
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Cytosine Deaminase / metabolism
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Drug Resistance, Neoplasm
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Female
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Flucytosine / pharmacokinetics
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Flucytosine / therapeutic use
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Genetic Therapy / methods*
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Genetic Vectors / genetics
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Glutathione S-Transferase pi
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Glutathione Transferase / genetics*
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Humans
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Isoenzymes / genetics*
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Ovarian Neoplasms / drug therapy
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Ovarian Neoplasms / genetics
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Ovarian Neoplasms / metabolism
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Ovarian Neoplasms / therapy*
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Pentosyltransferases / genetics*
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Pentosyltransferases / metabolism
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Polymerase Chain Reaction
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Promoter Regions, Genetic
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Xenograft Model Antitumor Assays
Substances
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Antineoplastic Agents
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Isoenzymes
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Recombinant Fusion Proteins
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Flucytosine
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Pentosyltransferases
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uracil phosphoribosyltransferase
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GSTP1 protein, human
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Glutathione S-Transferase pi
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Glutathione Transferase
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Gstp1 protein, mouse
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Cytosine Deaminase
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Cisplatin